Obermayr Eva, Koppensteiner Nina, Heinzl Nicole, Schuster Eva, Holzer Barbara, Fabikan Hannah, Weinlinger Christoph, Illini Oliver, Hochmair Maximilian, Zeillinger Robert
Molecular Oncology Group, Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
Department of Respiratory and Critical Care Medicine, Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Klinik Floridsdorf, Bruenner Strasse 68, 1210 Vienna, Austria.
J Pers Med. 2021 Nov 18;11(11):1225. doi: 10.3390/jpm11111225.
Despite recent advances in the treatment of non-small cell lung cancer (NSCLC), less than 10% of patients survive the first five years when the disease has already spread at primary diagnosis.
Blood samples were taken from 118 NSCLC patients at primary diagnosis or at progression of the disease before the start of a new treatment line and enriched for circulating tumor cells (CTCs) by microfluidic Parsortix™ (Angle plc, Guildford GU2 7AF, UK) technology. The gene expression of epithelial cancer stem cell (CSC), epithelial to mesenchymal (EMT), and lung-related markers was assessed by qPCR, and the association of each marker with overall survival (OS) was evaluated using log-rank tests.
EpCAM was the most prevalent transcript, with 53.7% positive samples at primary diagnosis and 25.6% at recurrence. EpCAM and CK19, as well as NANOG, PROM1, TERT, CDH5, FAM83A, and PTHLH transcripts, were associated with worse OS. However, only the CSC-specific NANOG and PROM1 were related to the outcome both at primary diagnosis (NANOG: HR 3.21, 95%CI 1.02-10.14, = 0.016; PROM1: HR 4.23, 95% CI 0.65-27.56, = 0.007) and disease progression (NANOG: HR 4.17, 95%CI 0.72-24.14, = 0.025; PROM1: HR 4.77, 95% CI 0.29-78.94, = 0.032).
The present study further underlines the relevance of the molecular characterization of CTCs. Our multi-marker analysis highlighted the prognostic value of cancer stem cell-related transcripts at primary diagnosis and disease progression.
尽管非小细胞肺癌（NSCLC）的治疗最近取得了进展，但在疾病初次诊断时已经扩散的患者中，不到10%能存活五年。
在初次诊断时或疾病进展且新治疗线开始前，从118例NSCLC患者中采集血样，并通过微流控Parsortix™（Angle plc，吉尔福德GU2 7AF，英国）技术富集循环肿瘤细胞（CTC）。通过qPCR评估上皮癌干细胞（CSC）、上皮-间质转化（EMT）和肺相关标志物的基因表达，并使用对数秩检验评估每个标志物与总生存期（OS）的关联。
EpCAM是最普遍的转录本，初次诊断时53.7%的样本呈阳性，复发时为25.6%。EpCAM和CK19，以及NANOG、PROM1、TERT、CDH5、FAM83A和PTHLH转录本与较差的OS相关。然而，只有CSC特异性的NANOG和PROM1在初次诊断（NANOG：HR 3.21，95%CI 1.02 - 10.14，P = 0.016；PROM1：HR 4.23，95%CI 0.65 - 27.56，P = 0.007）和疾病进展时（NANOG：HR 4.17，95%CI 0.72 - 24.14，P = 0.025；PROM1：HR 4.77，95%CI 0.29 - 78.94，P = 0.032）与预后相关。
本研究进一步强调了CTC分子特征的相关性。我们的多标志物分析突出了癌症干细胞相关转录本在初次诊断和疾病进展时的预后价值。
